Rationale: Substantial numbers of adolescents engage in moderate to heavy levels of alcohol consumption. Specifically, 44% of 12th graders have used alcohol in past month, and 26% have engaged in a binge drinking episode in the past two weeks (Johnston et al., 2008). Identifying the influence of adolescent alcohol use on brain functioning is important, as decrements incurred during ongoing neuromaturation could have lasting effects on cognitive functioning and future educational and occupational options. Visual working memory (VWM) is an essential component of information processing and executive functioning, and is therefore a useful probe for examining neural abnormalities associated with heavy adolescent drinking. Design: The aims of this investigation are: (1) to prospectively examine brain response to a VWM task in adolescents who transition into heavy drinking (n = 22) versus youth who remain non-users (n = 22) using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), and (2) examine if these neural abnormalities are associated with neuropsychological functioning. The proposed study uses data collected as part ofthe Sponsor's longitudinal study (fMRI and Cognition in Youth at Risk for Alcoholism, ROI AAI3419, 6/10/07-3/31/12), using data from 12-16 year-olds imaged prior to the onset of drinking as well as follow-up data collected after half transitioned to heavy drinking. Analyses employ Analysis of Functional Neuroimaging (AFNI) tools and conduct a group x time ANOVA on a priori specified regions of interest (right postcentral/inferior parietal, right middle frontal, bilateral medial frontal, and middle occipital regions) to see if youth who initiate heavy drinking show a change in activation pattern, as compared to youth who remain non-drinkers. Regions that show divergent activation in initiators of heavy drinking will be followed by examining correspondence to performance on neuropsychological measures of VWM and attention among the heavy drinkers (n = 22) in regression analyses. PUBLIC HEALTH RELEVANCE: This investigation will help clarify the effects of alcohol use on brain functioning during adolescence, and aid in understanding whether deficits in VWM result from alcohol involvement. Deficits in VWM could interfere with tasks requiring higher-order executive functioning. The long-term goals of this line of work are to (1) disseminate any findings through adolescent drinking prevention materials and public service campaigns, and (2) inform intervention and psychoeducational programs on how to optimally intervene with youth engaging in heavy drinking, considering brain response and neurocognitive patterns linked to adolescent alcohol use.